Migraine with aura: which patients are most at risk of stroke?

The complex association between migraine (M) and ischemic stroke (IS) is discussed. Epidemiological studies and meta-analyses show that M with aura (MA) and not M without aura, doubles the risk of IS. The risk is higher for female gender, young age and higher headache attacks frequency. Smoking habit and oral contraceptives, especially if associated, increase stroke risk. The underlying pathogenetic mechanisms are not completely understood, but it is hypothesized that a particular brain susceptibility to cortical spread depression could explain the association between MA and IS. The absolute risk of IS in migraineurs is relatively low and an antithrombotic primary prevention is not indicated, but it is mandatory to investigate and treat associated risk factors for IS and, in young MA women, consider only progestinic oral contraceptives, if needed, and smoking cessation.

Electroclinical evolution in ring chromosome 20 epilepsy syndrome: a case with severe phenotypic features followed for 25 years.

Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20 syndrome [r(20)], while dysmorphic features, mental retardation and behavioural disturbances are widely variable. The clinical evolution of r(20) over time is not well defined as relatively few cases have been reported. Here we describe a patient with severe clinical features followed for a 25-year period. The patient was subjected to clinical, psychometric and EEG evaluation twice a year from the age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence in situ hybridization (FISH) and several immunological investigations were performed. Ring chromosome 20 was found in 50% of examined metaphases with the deletion of subtelomeric regions 20p and 20q. Our patient presented with marked dysmorphic features, severe mental retardation, tetraparesis, dysarthria and intractable epilepsy with onset during the first year of life. During follow up, EEG findings and clinical features progressively worsened: a progressive disorganization of background EEG activity occurred and mental and motor impairment evolved. The severity of clinical expression depended on the extent of chromosomal deletion and on the haploinsufficiency of other important related genetic loci due to ring instability. The progressive worsening of both clinical and EEG features over a long period, which has also been reported by other authors, further characterized this syndrome.

Specific impairment of BAER's in Friedreich's ataxia. Auditory evoked responses in clinical evaluation and differential diagnosis.

We have investigated brainstem and cortical auditory responses (BAERs and CAERs) in 16 cases of Friedreich's ataxia (FA) and have compared the findings with those obtained in 2 cases of familial spastic paraplegia (FSP), in 5 cases of Charcot-Marie-Tooth disease (CMTD), and in 6 cases of atypical FA of uncertain classification. BAERs could not be elicited in 11 FA patients and constantly disappeared at a higher intensity threshold than in normal subjects in the remaining 5 patients. BAERs were normal or only slightly abnormal in FSP and CMTD patients. CAERs were normal in all 29 patients. BAERs tended to disappear with the progression of FA and BAER thresholds were correlated with the Inherited Ataxias Clinical Rating Scale score, which is an index of the severity of illness. BAERs contributed to the diagnosis, or exclusion of FA in patients with an atypical picture. It is suggested that in FA myelinated fibers in the spiral ganglion are partially affected, resulting in the decrease of wave amplitude such as occurs for peripheral sensory potentials.

Bioptically demonstrated Lafora disease without EPM2A mutation: a clinical and neurophysiological study of two sisters.

Lafora disease (LD) is an autosomal recessive inherited form of progressive myoclonic epilepsy with dementia and ataxia, usually presenting in the second decade of life and inexorably progressing until death. Neuropathological hallmarks are Lafora bodies, intracytoplasmic inclusions that can be found in neurons and in other tissues. LD gene (EPM2A), mapping on chromosome 6, encodes for a tyrosine phosphatase protein called laforin. However, up to 20% cases of LD are not genetically linked to chromosome 6. We report two sisters affected from bioptically diagnosed LD but without evidence of EPM2A mutation. Although familial cases of LD are already reported in literature, our observation leads to some considerations on clinical-electrophysiological evolution as well as to remark the genetic heterogeneity of this condition. In addition, we report the good effect of the Levetiracetam for the treatment of myoclonus in these patients, also demonstrated by the electrophysiological findings.

Residual reading capability in a patient with alexia without agraphia.

A case of pure alexia due to an ischemic lesion of the occipital temporal region is described. Written words could be matched but not read. Immediate memory span for graphemes was defective. The reading defect probably depends on the inability to modify the written word "globally"; the phonological process was intact, but the memory disturbance impeded reading. The dissociation is explained by the preservation of word forms, which are linked to the semantic stage. Non-written stimuli trigger a "meaning" which evokes the word form and so the written word is recognized even though it cannot be read.

[Clinical efficacy of picotamide]. / Efficacia clinica della picotamide.

The effects of picotamide (300 mg b.i.d.) for secondary prevention of cerebral ischemia were compared with the effects of low-dosage aspirin (300 mg/die). Out of the 87 randomized patients, 47 completed a six month period of treatment: 29 patients in the picotamide (group P) with a mean period of 14.5 months, 18 in the aspirin group (group A) with a mean period of 15.2 months. Both showed reduced incidence of further cerebral ischemic episodes in comparison with non treated patients (literature data). Using intention-to-treat analysis, the recurrence of ischemic events (including TIA) was 5.8% in group P and 14.3% in group A. Explanatory analysis yielded similar results: 10.3% of patients in group P and 27.8% in group A had recurrence of cerebral ischemic eposides. Evaluating as endpoints only RIND and stroke, the incidence was 10.3% in group P and 16.7% in group A. In conclusion, picotamide was more effective than aspirin; however the difference was not statistically significant due to the small number of patients. The drug was well tolerated and only two patients dropped out because of side effects. Picotamide did not alter laboratory tests significantly.

[Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome]. / Effetti del trattamento cronico con L-acetilcarnitina nella sindrome di Down.

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non-Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.

Correlation between hyperglycemia and cerebral infarct size in patients with stroke. A clinical and X-ray computed tomography study in 104 patients.

Infarct area size on CT scan in 104 patients with ischemic stroke was compared with blood glucose levels and with other biological parameters (arterial pressure, hematocrit, consciousness impairment, clinical picture) during the acute stage. Infarct size was also compared with the presence and severity of diabetes mellitus and other risk factors. Infarct size was significantly correlated with hyperglycemia in the acute stage (p = 0.0348), regardless of the presence of established diabetes. These findings support the hypothesis that hyperglycemia directly increases regional brain damage due to acute vascular insufficiency. Infarct size was also correlated with the presence of atrial fibrillation, consciousness impairment, severity of clinical picture and neurological outcome.

LGI1 microdeletion in autosomal dominant lateral temporal epilepsy.

OBJECTIVES: To characterize clinically and genetically a family with autosomal dominant lateral temporal epilepsy (ADLTE) negative to LGI1 exon sequencing test. METHODS: All participants were personally interviewed and underwent neurologic examination. Most affected subjects underwent EEG and neuroradiologic examinations (CT/MRI). Available family members were genotyped with the HumanOmni1-Quad v1.0 single nucleotide polymorphism (SNP) array beadchip and copy number variations (CNVs) were analyzed in each subject. LGI1 gene dosage was performed by real-time quantitative PCR (qPCR). RESULTS: The family had 8 affected members (2 deceased) over 3 generations. All of them showed GTC seizures, with focal onset in 6 and unknown onset in 2. Four patients had focal seizures with auditory features. EEG showed only minor sharp abnormalities in 3 patients and MRI was unremarkable in all the patients examined. Three family members presented major depression and anxiety symptoms. Routine LGI1 exon sequencing revealed no point mutation. High-density SNP array CNV analysis identified a genomic microdeletion about 81 kb in size encompassing the first 4 exons of LGI1 in all available affected members and in 2 nonaffected carriers, which was confirmed by qPCR analysis. CONCLUSIONS: This is the first microdeletion affecting LGI1 identified in ADLTE. Families with ADLTE in which no point mutations are revealed by direct exon sequencing should be screened for possible genomic deletion mutations by CNV analysis or other appropriate methods. Overall, CNV analysis of multiplex families may be useful for identifying microdeletions in novel disease genes.

Multiple cerebral aneurysms associated with atrial myxoma. A case report.

Cardiac myxoma is a tumor of mesenchymal origin accounting for half of all primary cardiac neoplasms. Intracranial involvement by atrial myxoma is a rare cause of neurologic deficit. When the myxoma arises in the left atrium, systemic emboli from a cardiac myxoma can lead to infarction, cerebral hemorrhage and aneurysm formation. In the light of the potentially preventable nature of these lesions, the diagnosis of myxomatous aneurysms should be considered in any patient with neurologic symptoms and a history of cardiac myxoma. Because aneurysms are often stable over several years, conservative management with careful clinical and radiological follow-up with MRI and angiography seems sensible. We describe a case in which MR imaging and angiography were used to diagnose multiple cerebral aneurysms caused by left atrial myxoma.

Unawareness of "illnesses": a case of right-sided hemiballism.

The Authors describe a non-demented patient who, after a left subthalamic haemorrhage causing hemiballism, was completely unaware of both neurological (i.e., dyskinesias) and non-neurological (i.e., cough) symptoms occurring after the stroke. In contrast, he was perfectly able to acknowledge pathological conditions affecting him before the brain damage. Neuropsychological assessment showed no cognitive defects, but revealed the presence of frontal behaviours (e.g., perseverations and utilization behaviours). This unusual clinical picture was ascribed to damage of frontal-subcortical circuits involved in conscious representation of current bodily states.

Recurrent Intraventricular Hemorrhages Caused by an AVM Detected by Angiography with Initially Normal Angiogram.

Primary intraventricular haemorrhage (PIVH) is an uncommon type of non-traumatic cerebral haemorrhage limited to the ventricular system arising in adults and children, with diverse aetiology and variable course. Vascular malformations account for 34% of PIVH, whereas no cause is found in 21-47%. When a primary intraventricular haemorrhage is detected in a young patient an underlying lesion such as an arteriovenous malformation (AVM) must be ruled out. The diagnosis may be suspected when there is sudden onset of headache, nausea and vomiting with or without a reduced level of consciousness. Nevertheless, even if clinical features suggest the diagnosis of PIVH, cerebral computed tomography (CT) scan is required for confirmation, and magnetic resonance imaging (MRI) and catheter angiography are necessary to establish the aetiology. We describe a case of isolated recurrent intraventricular haemorrhages caused by AVM detected by diagnostic intracranial angiography with no abnormality demonstrated on angiography four years earlier.

Sentinel headache.

Patients with subarachnoid haemorrhage (SAH) frequently describe the occurrence of an underestimated or even ignored severe headache in the days or weeks preceding the bleeding. If recognised early, this warning headache might lead to specific investigations and, if indicated, a surgical approach might avoid a dramatic haemorrhagic event. In a recent and exhaustive systematic review, the incidence of a sentinel headache (SH) was evaluated in a range of 10-43% of SAH patients. SH seems to be due to a minor bleeding from a leak of a berry aneurysm and usually occurs in the preceding two weeks. Such a period is similar to the one for rebleeding in SAH and supports the hypothesis of the warning leak. Nevertheless, a warning headache can precede a SAH in unruptured aneurysm even without a minor bleeding. Underestimation or misdiagnosis of SH depends on incorrect evaluation of the headache characteristics (unusual, severe, abrupt, thunderclap), overestimation of cranial CT sensitivity (false negative increasing over the elapsing time), failure to perform lumbar puncture (LP) in patients with negative CT, incorrect evaluation of CSF findings (xanthochromia may be absent in the first 12 h) and failure to differentiate traumatic tap from true SAH. Considering the diagnosis of SH in all cases of a severe, sudden-onset (thunderclap) headache, and performing all the appropriate diagnostic exams, including LP if necessary, could prevent subsequent massive bleeding and its invalidating or fatal consequences.

Otoneurological findings in Friedreich's ataxia and other inherited neuropathies.

Fifteen cases of Friedreich's ataxia (FA) were examined using an otoneurological test battery that included tone and speech audiometry, the synthetic sentence identification (SSI) test, impedance audiometry, cortical auditory-evoked response (CAER), brainstem auditory-evoked response (ABR) and electronystagmography. We also obtained ABR and CAER findings in 2 cases of familial spastic paraplegia, in 5 cases of Charcot-Marie-Tooth disease and 6 in cases of atypical FA of uncertain classification. The results of puretone and impedance audiometry were normal in all cases. ABR could not be elicited in 11 FA patients and were abnormal at higher intensity levels in the remaining 4 patients. In these 4 cases, however, the latencies were normal. ABR did not show any marked abnormalities in patients with familial spastic paraplegia or Charcot-Marie-Tooth disease. CAERs were normal in all 28 patients. ABRs tended to be absent with the progression of FA. ABR thresholds were correlated with the Inherited Ataxias Clinical Rating Scale score, which is an index of the severity of the illness. ABRs contributed to the diagnosis or to excluding FA in patients with an atypical clinical picture. The absence of ABRs and the normal latencies of the waves, when evoked, agree with the pathological finding of a reduction of fibers in the spinal root ganglion. SSI abnormalities and vestibular findings agree with this hypothesis.

Bilateral thalamic damage, cortical hypometabolism and behavioural disturbances.

Thalamic damage could be responsible for reduced metabolism in anterior cortical areas. In order to investigate an anatomical lesion and impairment of regional blood flow (rCBF) in distant cortical areas, we studied by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) a patient with bilateral thalamic infarction, who presented with sudden consciousness impairment, drowsiness, gaze paralysis, dysphagia and bilateral Babinski sign. Three weeks later the neurological symptoms disappeared, but a severe mental deterioration was evident MRI showed thalamic bilateral damage of posterior and medial areas, involving part of the pulvinar, more evident for the right thalamus. A (99m) Tc-HMPAO SPECT showed a decrease of rCBF over frontal and parietal regions, more evident for the right hemisphere. Six months later a severe memory impairment was still evident and MRI and SPECT picture were unchanged. The persistent memory defect could be related to a loss of cortical activation following the thalamic damage. The absence of primary lesions of cortical regions on CT scan and MRI and the neuroanatomical considerations on the diffuse projections running from medial nuclei and pulvinar to large parts of anterior neocortex supported this hypothesis.

EEG and spectral analysis in HIV immunocompetent patients free from clinical CNS impairment. A follow-up study in 20 cases.

Twenty HIV immunocompetent subjects without neurological symptoms were studied by EEG and spectral EEG analysis over a period of 6-16 months. 40% of them showed mild diffuse changes in background activity on basal evaluation, but the appearance of neurological symptoms and the evolution of clinical picture seemed unrelated to the presence of aspecific EEG and spectral analysis changes. As most of them were oppiate abusers, these findings could be ascribed to the long-term drug use.

Photoparoxysmal response on eye closure in photosensitive patients.

The Authors studied the presence of photoparoxysmal response (PPR) during intermittent photic stimulation (IPS) in 2,888 consecutive EEG recordings. PPR was present in 2.3% of EEGs and 10% of all patients referred to EEG laboratory for epilepsy (45 patients, 18 males, 27 females (M:F ratio 1:1.5), mean age 12 yrs). In 24 (53.3%) of these patients PPR was evident only (24.4%) or strikingly (28.9%) on eye closure during IPS. In 7 patients no other epileptic abnormalities were found on basal EEG and during hyperventilation, nor during IPS with eyes closed and with eyes open. The Authors consider the eye closure during IPS the most useful method to reveal a PPR in photosensitive patients and believe that a good IPS technique must include this procedure in the routine EEG examination.

Calcium antagonist nimodipine in intractable epilepsy.

The influx of Ca2+ into the neuron seems to play an important role in the genesis of epileptic seizures, and current research suggests that calcium entry blockers may have anticonvulsant activity. We used nimodipine, a calcium antagonist with high central nervous system affinity at a fixed dosage of 30 mg, t.i.d., in 21 patients with intractable epilepsy caused by organic brain lesions in addition to basal antiepileptic drug (AED) therapy. After a 12-week treatment period 14 patients (67%) showed a decrease in seizure frequency, four patients had no change, and three had an increase. In eight patients (38%) seizure frequency decreased by greater than 40%. The p value with one-tailed t-test was 0.0491. No significant modifications in AED or electrolyte serum levels were found. One patient had a lowering of blood pressure at this dosage.

EEG findings in West syndrome a follow-up of 20 patients.

Clinical and EEG findings of 36 patients with West syndrome (WS) were reported. Twenty patients (7 males, 13 females; mean age 7.4 months at the first EEG examination) were followed for a mean period of 19.3 months. Fifty per cent of the 8 cases with cryptogenic SW showed a full recovery, 2 cases showed persistence of psychomotor retardation or seizures and 2 of both these features. At the end of follow-up period, 92% of the 12 patients with symptomatic WS showed a psychomotor retardation and 75% a persistence of seizures. EEG pattern was a typical hypsarrhythmic one in 11 patients and atypical in the remaining cases. The typical pattern correlated with a better outcome with full recovery in 27.3% compared with 11.1% in the group with atypical EEG. Moreover EEG monitoring was useful for the evaluation of therapeutic response and in the follow-up of the disease, showing a correlation with clinical course, incidence of spasms and outcome.